Prophylactic cranial irradiation is indicated following complete response to induction therapy in small cell lung cancer: results of a multicentre randomised trial. United Kingdom Coordinating Committee for Cancer Research (UKCCCR) and the European Organization for Research and Treatment of Cancer (EORTC)

Prophylactic cranial irradiation (PCI) reduces the risk of cranial metastasis in small cell lung cancer (SCLC), but the magnitude and value of this reduction, the risks of radiation morbidity and whether PCI influences survival are unclear. We conducted a randomised trial in patients with limited-stage SCLC who had had a complete response to induction therapy. Initially, patients were randomised equally to (1) PCI 36 Gy in 18 daily fractions, (2) PCI 24 Gy in 12 fractions and (3) no PCI; subsequently, to increase the rate of accrual, randomisation was to clinicians' choice of PCI regimen versus no PCI (at a 3:2 ratio). The endpoints were appearance of brain metastases, survival, cognitive function, and quality of life (QoL). Three hundred and fourteen patients (194 PCI, 120 No PCI) were randomised. In the revised design, the most commonly used PCI regimens were 30 Gy in 10 fractions and 8 Gy in a single dose. With PCI, there was a large and highly significant reduction in brain metastases (HR = 0.44, 95% CI 0.29-0.67), a significant advantage in brain-metastasis-free survival (HR = 0.75, 95% CI 0.58-0.96) and a non-significant overall survival advantage (HR = 0.86, 95% CI 0.66-1.12). In both groups, there was impairment of cognitive function and QoL before PCI and additional impairment at 6 months and 1 year, but no consistent difference between the two groups and thus no evidence over 1 year of major impairment attributable to PCI. PCI can safely reduce the risk of brain metastases. Further research is needed to define optimal dose and fractionation and to clarify the effect on survival. Patients with SCLC achieving a complete response to induction therapy should be offered PCI.

Appendiceal perforation, pneumoperitoneum, and Hirschsprung's disease.

In this report, we describe an infant with appendiceal perforation due to total colonic Hirschsprung's disease, to emphasize this rare but important presentation of Hirschsprung's disease. Based on our own experience and a survey of similar cases, we suggest that an underlying etiology, namely long-segment Hirschsprung's disease, should be suspected in infants with a perforated appendix, especially when a radiographic pneumoperitoneum is present. Prompt diagnosis and appropriate therapy is essential in this situation to prevent morbidity and mortality.

Bowel perforation in Hirschsprung's disease.

A review of the medical records of 45 infants less than 1 year old with Hirschsprung's disease identified two (4.4%) who presented with bowel perforation. A literature survey was done to evaluate the relationship between bowel perforation of the bowel early in the course of Hirschsprung's disease indicates that: the infant under 4 months old is at the greatest risk; the majority of cases (62%) were associated with long-segment or total colonic Hirschsprung's disease; the most common sites of perforation were the proximal colon (68%) and appendix (17%); in cases with a short or intermediate length of aganglionic bowel, the perforation was proximal to or at the site of transition, but in 84% of infants with total colonic aganglionosis the perforation was situated in aganglionic bowel. Hirschsprung's disease should be a prime differential consideration in a young infant with penumoperitoneum caused by distal bowel perforation.

The effect of adjuvant chemotherapy on relapse-free survival in patients with osteosarcoma of the extremity.

We conducted a randomized controlled trial to determine whether intensive multi-agent adjuvant chemotherapy improves the chances of relapse-free survival in patients with nonmetastatic high-grade osteosarcoma of the extremity, as compared with concurrent controls. After undergoing definitive surgery, 36 patients were randomly assigned to adjuvant chemotherapy or to observation without adjuvant treatment. At two years the actuarial relapse-free survival was 17 percent in the control group, similar to that found in studies before 1970, and 66 percent in the adjuvant-chemotherapy group (P less than 0.001). Similar results were observed among 77 additional patients who declined to undergo randomization but who elected observation or chemotherapy. We conclude that the natural history of osteosarcoma of the extremity has remained stable over the past two decades, that adjuvant chemotherapy increases the chances of relapse-free survival of patients with high-grade osteosarcoma, and that it should be given to all such patients.

Imaging procedures in pediatrics.

To demonstrate the use of these multiple techniques, one might consider algorithms that are available for various disorders. It is worth pointing out that for imaging of specific abnormalities, they must be evaluated in light of the skill and interest of available personnel and on the equipment that is available. For example, in acute upper abdominal trauma in children the following is one diagnostic route: With no substantial suspicion of brain injury and after evaluation by an attending surgeon; With upper abdominal injury limited reasonably clearly to the kidneys, renal vessels, and ureters: Intravenous sonography; With upper abdominal injury limited reasonably clearly to the liver, spleen, or both: Liver/spleen scintigraphy; With substantial suspicion that the injury is not limited to the kidneys or the liver and spleen: Enhanced CT of upper abdomen; With a suspicion of brain injury sufficient to require CT of the head: CT scan, and if there is abdominal injury as well, contrast enhanced CT of the upper abdomen; Again it is to be emphasized that this diagnostic route (as well as the ones in Figures 1 and 2) represents an approach and is used in the context of this chapter to illustrate the role of the various imaging techniques that are available to the diagnosis of one pediatric problem.

Alternate-day prednisone reduces morbidity and improves pulmonary function in cystic fibrosis.

A randomised, double-blind, placebo-controlled study examined the effects of alternate-day prednisone therapy on morbidity and progression of lung disease in cystic fibrosis (CF). At baseline the patients (aged 1-12 years) had mild to moderate lung disease, and the prednisone group did not differ significantly from the placebo group for any values measured. After 4 years, the prednisone-treated group had significant advantages over the placebo group for height, weight, vital capacity, forced expiratory volume in 1 s, peak flow rate, erythrocyte sedimentation rate, and serum IgG. The prednisone-treated group required 9 admissions to hospital for CF-related pulmonary disease compared with 35 for the placebo group. There were no steroid-induced side-effects. To rule out bias in case selection, 69 CF clinic patients comparable in age and clinical status but not included in the study were compared with the placebo group at 4 years; no significant differences between the groups were found.

Elevated nephrogenous cyclic adenosine monophosphate to monitor early renal osteodystrophy.

Radiographs, serum chemistries, parathyroid hormone (PTH), and nephrogenous cyclic adenosine monophosphate (cAMP) were evaluated in thirty-two children with normal serum creatinine, chronic renal insufficiency, chronic hemodialysis, and transplantation. Nephrogenous cAMP increases linearly with creatinine, and there is a good correlation (r = 0.89) between immunoreactive PTH (iPTH) and nephrogenous cAMP except for patients with severe renal insufficiency or requiring chronic hemodialysis. Elevated nephrogenous cAMP is evidence for metabolic bone disease earlier than usually recognized. Early measurements of iPTH and nephrogenous cAMP could ensure early therapeutic intervention which might alleviate renal osteodystrophy in chronic renal insufficiency and transplant patients.

Diagnosis of ectopic thyroid: value of pretracheal soft-tissue measurements.

Thyroid ectopia, dysgenesis, or agenesis has been conventionally diagnosed with the use of radioisotope scanning procedures. This report proposes the use of a conventional lateral radiograph of the neck to determine the presence or absence of the thyroid gland in its normal anatomic position. The thyroid gland is ensheathed by the pretracheal layer of the deep cervical fascia anterior to the trachea. The gland's presence or absence can be determined by calculating the ratio of the soft-tissue measurements between the anterior wall of the trachea and both the outer margin of the skin and the margin of the subcutaneous fat as determined from a lateral radiograph of the neck. This "pretracheal ratio" may be used to accurately differentiate between a lingual thyroid and other masses at the base of the tongue.

An improved radionuclide method for the diagnosis of gastroesophageal reflux and aspiration in children (milk scan).

A radionuclide study using technetium-99m-labelled milk feeding is described for the detection of gastroesophageal reflux and aspiration in children. A comparison of findings in 39 patients referred for both radiographic and radionuclide studies showed that barium studies were positive in 25.6% and radionuclide studies in 59% of cases, reflecting the sensitivity of the radionuclide technique. This technique is also physiological and allows prolonged patient monitoring. It is simple to perform and should prove useful in the evaluation of patients suspected of having gastroesophageal reflux and aspiration.

Krypton-81m: a better radiopharmaceutical for assessment of regional lung function in children.

Krypton-81m, an inert, radioactive gas with a physical half-life of 13 seconds was used to evaluate regional lung ventilation in 25 pediatric patients. The results suggest that Kr-81m has several advantages over previous methods employing xenon-133. These include: more favorable physical characteristics for imaging with present scintillation cameras; ease of performance of the examinations; improved resolution and multiple views with better detection and localization of abnormalities; and a much lower dose to the patient.